Ethics of using

convalescent whole blood and convalescent

plasma during the Ebola epidemic

Interim guidance for ethics review committees, researchers,

national health authorities and blood transfusion services
© World Health Organization 2015

All rights reserved.

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WHO/HIS/KER/GHE/15.1 (Version 1.0)

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | ii
Acknowledgements
The creation of the present guidance would not have been possible without the participation of
numerous individuals and groups.

The development of this interim guidance was led by Marion Danis (USA) and Ogobara Doumbo
(Mali) of the Ethics Working Group and WHO staff Carla Saenz (AMRO/KBR). It was strengthened
by the input provided by other members of the Ethics Working Group, which was established by the
Global Health Ethics Unit to address the ethical issues arising in the context of the Ebola epidemic
(see Appendix 1). We would also like to acknowledge the essential contributions of WHO staff
Marie-Charlotte Bouësseau (HQ/SDS) and the valuable background literature provided by Emmanuel
Streel.

The review and finalization of the document was coordinated by Abha Saxena and Vânia de la
Fuente-Núñez of the WHO-HQ Department of Knowledge, Ethics and Research.

The final document was further strengthened by the review provided by various WHO departments
and networks, including the WHO-HQ Departments of Service Delivery and Safety, of Global
Capacities Alert and Response, of Pandemic and Epidemic Diseases, and of Essential Medicines and
Health Products; and WHO-AFRO Divisions of Health Systems and Services & Immunization,
Vaccines and Emergencies. It also includes comments from WHO Global Blood Safety Network;
WHO Experts on Blood Transfusion Medicine and Biological Standardization from Bhutan,
Cameroun, Hong Kong SAR, China, Ghana, Honduras, Italy, Malaysia, New Zealand, Singapore,
South Africa, UK and USA; WHO Blood Regulatory Network; WHO-AMRO/PAHO Division of
Health Systems and Services; Centers for Disease Control and Prevention, Atlanta; International
Severe Acute Respiratory and Emerging Infection Consortium; African Society for Blood Transfusion;
International Council for Commonality in Blood Bank Automation (ICCBBA); European Blood
Alliance; International Society of Blood Transfusion; and American Association of Blood Banks
(AABB). The contribution of WHO staff members David Wood (HQ/EMP), Neelam Dhingra-Kumar
(HQ/SDS) and Asiya Ismail Odugleh-Kolev (HQ/GCR) in the development and review of this
document is particularly acknowledged.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | iii
Contents
1. Background 1

2. Ethically relevant facts 1

2.1. Context constraints 1

2.2. Uncertain therapeutic efficacy of convalescent whole blood and convalescent plasma 2
2.3. Uncertain therapeutic safety of convalescent whole blood and convalescent plasma for
people with Ebola virus disease 2
2.4. Medical and psychosocial condition of convalescent people 2

3. Ethical analysis and recommendations 3

3.1. Gathering evidence 3

3.2. Disseminating results 4
3.3. Community engagement 4
3.4. Donors and recipients as research participants 5
3.5. Ethical oversight 5
3.6. Donor-related issues 5
3.7. Recipient-related issues 8
3.8. Issues related to health workers and research and ancillary staff 11

4. References 12

Appendix I 15

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | iv
1. Background
WHO convened a Consultation on Potential Ebola Therapies and Vaccines in Geneva, Switzerland on
4–5 September 2014. In the absence of proven treatments, participants widely agreed that
convalescent whole blood and convalescent plasma, among other experimental interventions, should
be considered for use for people with Ebola virus disease. Any such use should be scientifically
studied through carefully designed research studies. If, however, convalescent whole blood and
convalescent plasma are used for treating people with Ebola virus disease outside research studies,
this use should be considered “monitored emergency use of unregistered and experimental
interventions”, a term coined by WHO in the context of the current Ebola outbreak to refer to an
exceptional use of experimental interventions outside clinical trials, and to reflect the urgent need to
collect data on their efficacy and safety (1,2).1

This document specifically analyses the ethical issues surrounding the potential use and study of
convalescent whole blood and convalescent plasma in both research and clinical settings.

2. Ethically relevant facts

2.1 Context constraints

The Ebola epidemic is occurring in countries in western Africa that are not adequately prepared to
respond. Standard operating procedures for using convalescent whole blood and convalescent plasma
among people with Ebola virus disease do not exist. The current situation in the affected countries is
as follows.

 They lack the functional health care systems necessary to treat the people who are sick and
adequate public health systems and personnel to prevent the spread of Ebola virus disease.

 There is poor public understanding of Ebola virus disease, which has sparked rumours and fears
about its causes and treatment and has led to a lack of compliance with recommended infection
control practices, such as safe burials.

 There is an insufficient number of health-care workers to provide care. These countries faced
critical human resource shortages in the health sector before this outbreak, and Ebola virus disease
has taken a high death toll on this population subgroup: health-care workers who become infected
have an estimated case fatality rate of 59% (3). This critical shortage, the lack of adequate training
and protective equipment for health-care workers and the widespread public distrust of health
officials and health-care workers tremendously affect their commitment to work and reduce the
number of health-care workers per capita. This further complicates efforts to control the epidemic.

 The availability of basic blood transfusion services in some of the affected countries could ease
the use of convalescent whole blood or convalescent plasma for Ebola virus disease. However,
collecting, processing and using convalescent whole blood and convalescent plasma are more
challenging than routine blood transfusion activities because of (1) the risks associated with
contact with people with Ebola virus disease during blood transfusion and (2) the difficulties of
maintaining a registry of people with Ebola virus disease who have recovered, especially those

1
Monitored emergency use of unregistered interventions may be achieved through existing regulatory mechanisms that
contemplate the use of unregistered interventions under specific emergency circumstances, such as the notion of emergency
use of an investigational new drug by the United States Food and Drug Administration.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 1
 who live in remote and hard-to-reach areas and (3) the limited feasibility of obtaining blood or
plasma donations from donors in the midst of overwhelmed health-care systems with limited
infrastructure capacity and human resources.

2.2 Uncertain therapeutic efficacy of convalescent whole blood and convalescent

Plasma for people with Ebola virus disease

It is unknown whether convalescent whole blood and convalescent plasma can effectively treat
patients with Ebola virus disease. There is theoretical reason to expect that antibodies in the blood or
plasma of individuals who have survived Ebola virus disease would reduce the viral load of
individuals who are acutely ill due to the virus, but this remains unproven.

Transfusion of immune plasma is a standard therapy for South American haemorrhagic fevers caused
by arenaviruses, and it has been used successfully for treating people infected with other infectious
agents (4). For instance, in Hantavirus infection, convalescent plasma was safe and reduced the case
fatality rate to 14% in 29 treated cases versus 32% in 199 untreated cases (5). Nevertheless, only
anecdotal evidence suggests the possible efficacy of convalescent plasma (6), and evidence of the
efficacy of convalescent whole blood among patients with Ebola virus disease is disputed (7,8). Some
existing experimental data have even indicated the absence of efficacy of immune plasma and of
whole blood transfusions in non-human primates infected with various filovirus strains (which include
Ebola viruses) (9–11). However, monoclonal antibody cocktails (12–14) and immunoglobulin
preparations from vaccinated and challenged monkeys (15) have been effective in preventing Ebola
virus disease and treating monkeys with Ebola virus disease in the monkey challenge model.

2.3 Uncertain therapeutic safety of convalescent whole blood and convalescent

plasma for people with Ebola virus disease

The safety of convalescent whole blood and convalescent plasma therapies for people with Ebola
virus disease is not fully known, and there is a theoretical concern and some experimental evidence
about antibody-dependent enhancement of Ebola virus infection when these therapies are used in cell
culture (16). However, the use of convalescent whole blood and convalescent plasma for other
conditions is generally considered safe if standard precautions (17) and blood safety strategies are
effectively implemented, such as screening donated blood for transfusion-transmissible infections.
Thus, if these precautions and strategies are followed, and donors are people who have fully recovered
from Ebola virus disease (18), 2 transfusing convalescent whole blood or convalescent plasma for
treating patients with Ebola virus disease is expected to be safe.

2.4 Medical and psychosocial condition of convalescent people

People convalescing from Ebola virus disease often remain ill for weeks after recovering from the
acute phase: residual fatigue, poor nutritional status and joint pain are common (19). More severe
complications can also be seen, associated with immune recovery (20,21).

In addition, they may be affected by long-lasting mental distress because of the trauma of isolation in
Ebola treatment facilities, survivor’s guilt, social stigma, the loss of relatives or close friends, material
losses and rejection by their community (22–25).

2
To be released from care and eligible to donate, these patients should have a negative result on reverse-transcriptase
polymerase chain reaction (RT-PCR) on two blood samples (drawn 48 hours apart).

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 2
All these conditions make convalescents especially vulnerable to even slight coercion or to additional
physical burdens if blood donations are to be considered.

3. Ethical analysis and recommendations

The WHO Ebola Ethics Working Group emphasizes that priority should be given to providing basic
supportive care to everyone with Ebola virus disease and to preventing the spread of the epidemic. For
the sake of efficiency, and to maximize the benefits of efforts, interventions with known benefits
should be given priority. In the context of experimental interventions, for the sake of fairness, priority
should be given to studying promising interventions that (if proven to be safe and effective) could
reach the most affected individuals and prevent the greatest number of people from becoming infected
or save the lives of people with Ebola virus disease. Given the high mortality resulting from Ebola
virus disease and the absence of proven cures and vaccines, providing people with a potentially
beneficial intervention – such as convalescent whole blood or convalescent plasma – is ethical, even if
its efficacy is unknown (1). The ethical acceptability of providing convalescent whole blood or
convalescent plasma is partly supported by the presumed positive risk–benefit balance of these
therapies when standard blood safety strategies are being implemented – that is, the risks of negative
side effects are considered low when blood safety measures are in place, and theoretical and some
anecdotal evidence indicates that people with Ebola virus disease may benefit from these therapies. In
addition, the WHO Ebola Ethics Working Group considers that the following issues are ethically
relevant in providing convalescent whole blood and/or convalescent plasma to people with Ebola
virus disease.

3.1 Gathering evidence

In its deliberations on 21–22 October 2014, the WHO Ebola Ethics Working Group reiterated that (2):

There is an ethical imperative to carry out research on potential therapeutic agents against Ebola virus
disease.

Even in the context of a public health emergency, unregistered and experimental drugs and therapeutics
must be tested for safety and efficacy using rigorous methods and simple but properly designed clinical
trials. In the context of the current Ebola epidemic in West Africa, WHO has already published
recommendations that it is ethical to make investigational therapeutics available outside of clinical trials
for “emergency use” provided clinical data from their use is systematically collected and shared. Such
“emergency use” should not preclude or delay the initiation of more conclusive investigations of the
intervention in properly designed clinical studies. The latter, if appropriately designed and executed, may
yield generalizable conclusions that result in greater societal benefit.

The WHO Ebola Ethics Working Group proposed that the term “monitored emergency use of
unregistered and experimental interventions (MEURI)” should be used in this case instead of
“compassionate use” – a term that can have other meanings, such as use of an investigational intervention
for patients outside of an ongoing clinical trial or the indicated scope of utilization.

It is therefore ethically imperative to learn whether convalescent whole blood and convalescent
plasma are safe and efficacious for treating people with Ebola virus disease through carefully
designed and executed research studies. All efforts must be made to systematically gather relevant
data. This includes collecting safety data from transfusions of convalescent whole blood and
convalescent plasma, whether under research or monitored emergency use of unregistered and
experimental interventions, analysing these data and making them publicly available in an expedited
manner without compromising standard and supportive care, donor or recipient confidentiality or

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 3
health worker safety. Most crucially, immediate action should be taken locally and internationally to
respond to the new risk–benefit information that results from research related to convalescent whole
blood and convalescent plasma and to other experimental Ebola interventions. Examples include
closing clinical trials or treatment in the context of monitored emergency use of unregistered and
experimental interventions if relevant evidence is presented of harm to the donor or the person with
Ebola virus disease.

3.2 Disseminating results

Whether such treatment is successful or unsuccessful and whether it is part of research or monitored
emergency use of unregistered and experimental interventions, the results should be disseminated as
widely as possible to maximize their value in the Ebola epidemic. An important priority in the
dissemination plan is to provide for communication in a differentiated form with all relevant
audiences, including donors, people with Ebola virus disease receiving convalescent whole blood or
convalescent plasma, clinical practitioners and the wider public. People with Ebola virus disease and
other stakeholders should also be updated as the trial proceeds and promptly informed on the results
obtained.

3.3 Community engagement3

Engagement with local communities may be challenging in the context of the Ebola epidemic but is of
paramount importance to ensure fair processes in developing and implementing convalescent whole
blood or convalescent plasma programmes. This means that stakeholders should have a fair
opportunity to participate in deliberations about the future of the community and in the decisions that
may affect their lives. Communities should understand the rationale behind interventions with
convalescent whole blood and/or convalescent plasma, be involved in developing these programmes
and be able to decide whether these therapies are locally acceptable. Community engagement should
start early and be as inclusive as possible. The role of families in engagement practices should also be
considered, especially since they may be able to offer even more compelling reasons for individuals to
cooperate with their community and health systems. However, familial coercion is a concern and
should not be ignored (see section 3.6.1).

Community engagement processes need to identify the best ways of conveying not only the
uncertainty inherent in research but also seemingly contradictory messages: that contact with the body
fluids of a person with Ebola virus disease will transmit the disease and must be avoided, but
transfusion of blood from someone who has recovered from Ebola virus disease is safe, if the donors’
blood is properly screened for infections and is compatible with that of the recipients, and might help
treat the people with the disease. All efforts should be made to avoid misunderstandings, since they
can potentially lead to increased contagion, fuelling public distrust of officials and health-care
workers, and creating even more difficulty in controlling the spread of the epidemic. This is especially
important in the context of the affected populations, in which anxiety about blood theft, sale and
vampirism is not uncommon (26).

Communication efforts should also consider relevant cultural issues, since these may affect the
acceptability of donation in communities. For instance, community engagement strategies could
consider incorporating an educational component to address the fears of people who have recovered

3
WHO interim guidance on community engagement and education, recruitment and retention of people recovered from
Ebola as potential blood donors for convalescent blood and plasma (being developed) will provide further information on
WHO recommendations on community engagement practices.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 4
from Ebola virus disease. Given the current stigma attached to Ebola virus disease, community
engagement could additionally provide an opportunity to foster understanding in the community about
the disease and facilitate the reintegration of survivors into the community. As the number of people
who have recovered from Ebola virus disease grows, they should be encouraged to help in leading
community engagement efforts. For example, survivors could take an advisory role in ethics review
committees reviewing trials using convalescent whole blood and convalescent plasma.

Once convalescent whole blood and convalescent plasma start being collected, requests will probably
be made for sharing this resource across national borders. As an act of solidarity, sharing convalescent
whole blood and convalescent plasma seems to be a laudable practice, but there are potential safety
and product liability issues as well as ethical concerns related to ownership, fairness and justice that
need to be analysed further. As recently introduced in Europe, setting up an international panel of
experts in infectious diseases and transfusion medicine that includes ethicists should be encouraged to
address these issues in a practical and timely way.

3.4 Donors and recipients as research participants

Convalescent whole blood or convalescent plasma should preferably be used within a framework of
research (see section 3.1), without compromising health worker safety or the health care provided in
the health facility. In the research setting, the donor’s plasma might be subjected to further scientific
investigations (such as for anti-Ebola antibody titres), and both the donor and the recipient would
become research participants; this needs to be clearly explained to them prospectively so that they can
voluntarily decide whether they want to participate. Participants’ right (both donors’ and recipients’)
to withdraw from the study at any time without penalty or loss of benefits (such as standard of care)
should also be clearly communicated.

3.5 Ethical oversight

Even though the Ebola outbreak constitutes a public health emergency, any research that is
undertaken must adhere to high ethical standards. Local ethics committees should therefore provide
rigorous ethical review for research protocols and should seek assistance from international and other
organizations when needed For example, to help assess the technical and scientific validity of newly
proposed study designs. In turn, international and other organizations have a moral duty to provide
such assistance to local ethics committees in a timely manner. Similarly, the use of convalescent
whole blood or convalescent plasma outside research should be governed by the ethical principles of
non-maleficence, beneficence, justice and respect for persons.

3.6 Donor-related issues

This section outlines ethical issues related to donors of whole blood or plasma, whether they are asked
to donate for a research study or as part of monitored emergency use of unregistered and experimental
interventions.

3.6.1 Autonomy
3.6.1.1 Voluntariness

All blood and plasma donation should be voluntary and non-remunerated (27,28). A strictly
voluntary approach to blood donation is consistent with emphasizing the importance of
donors’ altruistic contribution and the principle of human dignity insofar as not using a
human body or its parts as a source of financial gain (29). Identifying donors of convalescent

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 5
 whole blood or convalescent plasma may be straightforward during the epidemic, since
potential donors are likely to have been treated in a facility for treating people with Ebola
virus disease. One might ask survivors when they leave a treatment facility whether they
would be willing to volunteer to donate blood or plasma after they have fully recovered. Such
a request should be done in a manner that does not exert undue pressure; for example, by
providing counselling services.

3.6.1.2 Obtaining informed consent4

An informed consent process for donors is essential both for research studies and as part of
the monitored emergency use of unregistered and experimental interventions. Potential donors
should be well informed about the rationale for donating their blood or plasma, the potential
benefit of their donation to other people with Ebola virus disease and the risks connected with
the procedure to them so that they can make informed decisions. For illiterate donors, a
witness should be present during the informed consent process. Where applicable, potential
donors should also be informed that they could be contacted again for further donations, and
they need to be given the option to opt out at any time.

3.6.1.3 Avoiding coercion and exploitation

Respecting donor autonomy also means that potential donors should be neither coerced nor
exploited. In the context of donating convalescent whole blood and convalescent plasma,
coercion refers to threatening people who have recovered from Ebola virus disease to donate,
whereas exploitation refers to any practice leading to an unfair distribution of the burdens of
and benefits from donation. An example of exploitation is accepting repeated donations from
one person who has recovered from Ebola virus disease irrespective of his or her health
status. Since the demand for convalescent blood and plasma may exceed the supply and the
intervention has the potential to save lives, communities and families are likely to have huge
expectations from people who have recovered from Ebola virus disease. Several options exist
to protect people convalescing from Ebola virus disease from undue pressure, coercion and/or
exploitation to donate.

o Independent counsellors could be made available to approach potential donors and

provide them with relevant donation-related information in a neutral manner
regarding the individual risks of donation, the use of donations, community benefits
and the voluntary nature of donation, so that donors can – if they so wish – refuse a
donation without feeling pressured or obliged to accept becoming a donor.
o Donors’ safety should be scrupulously safeguarded, especially through setting limits
on the age of the donor, the quantity of blood to be donated at one time and the
interval between subsequent donations to avoid compromising the potentially fragile
health of people convalescing from Ebola virus disease. The criteria for assessing
donor suitability should be based on WHO guidelines and effectively implemented.
Donors’ well-being should be sought and monitored for, and donation-related injuries
and adverse reactions should be promptly managed and recorded.

4
For an example of an informed consent form for the donation of convalescent whole blood or plasma to treat Ebola virus
disease, please refer to the WHO technical interim guidance on use of convalescent whole blood or plasma collected from
patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks (30).

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 6
 o Sites should consider banking convalescent whole blood and convalescent plasma
donations rather than giving them directly to patients with Ebola virus disease. This
would help protect the identity of donors and prevent exploitative practices.
o Communities and families should be informed that the blood of every person
convalescing from Ebola virus disease may not be useful and that certain tests may be
required to ascertain the usefulness of a blood donation. Such messages could protect
people convalescing from Ebola virus disease who voluntarily decide not to donate
blood or plasma or who are otherwise unfit for donation from possible harassment by
community members.

3.6.2 Fair selection of donors

Donations from people who have recovered from Ebola virus disease should only be accepted when
the donation is considered safe for the donor and when mechanisms are in place to guard against the
exploitation of potential donors. This should be rigorously assessed by a competent health-care
worker.

Children

The minimum age of donation should be in accordance with international guidance on blood donation
and national legislation on consent. Because children are at increased risk of vasovagal reactions and
adolescents have higher iron requirements, children who have recovered from Ebola virus disease
should in principle be excluded from donation (in accordance with WHO guidelines for donor
selection (31)) due to a lower benefit–risk ratio. If there are a disproportionately high number of
people who have recovered from Ebola virus disease within this age group, however, relaxing the
minimum age of donation to include minors older than 16 years of age may be ethically permissible
if: (1) the minors fulfil the standard physical and haematological criteria required for blood donation
and (2) the minors and their parents provided appropriate informed consent. Minors should be able to
fully comprehend, be properly informed and agree to the donation of blood and/or plasma, and their
parents or guardians should not overrule their decision regarding donation.

Other persons with diminished autonomy5

The acceptance of individuals with diminished autonomy (e.g., individuals with current or recurring
mental health problems) as blood donors should depend on (1) an assessment of their ability to give
informed consent to the donation process, including the testing of their blood (31), and (2) the
existence of sufficiently robust mechanisms to ensure that donors with diminished autonomy are
neither coerced to donate or subject to exploitative practices. Such mechanisms could include an
ethics committee that reviews these requests on a case-by-case basis. Where the criteria above are
met, both the individual with diminished autonomy and a family member or legal representative
should provide appropriate informed consent.

3.6.3 Confidentiality

The identities of people who have recovered from Ebola virus disease must be carefully protected
from wider disclosure to protect individual freedom to refrain from donation. Likewise, transfusion
should be anonymized, which means that the identities of donors and recipients should be

5
An individual is considered to have diminished autonomy when he/she has restricted capability of deliberation about
personal goals and limited ability to act under the direction of their deliberations.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 7
confidential. To do this, sites should consider storing the donated blood and plasma rather than
conducting one-to-one transfusion services with direct donation of blood or plasma to a specific
person such as family members or friends (see also section 3.6.1.3 above). To further protect the
confidentiality of donors, treatment centres should store blood and plasma units using only ID
numbers instead of identifiable information and ensure adequate disposal of unused units. Access to
areas where confidential donor, patient or staff records are stored should be restricted to authorized
staff (32).

3.6.4 Reimbursement for donation

Donation is considered an act of solidarity, compassion and altruism, and there is international
agreement that individuals should not receive payment for donating blood or plasma (33). 6
Nevertheless, reimbursing donors for any expenses directly associated with donation, such as travel
expenses, is reasonable. 7 In the context of Ebola virus disease, other non-financial forms of
recognition such as public recognition of donors as community heroes and dietary supplementation –
especially for repeated donors – could also be considered depending on the context. At a different
level, people who have recovered from Ebola virus disease may be in a desperate financial situation
themselves (23,24) and may demand payment for their donation of blood or plasma, thereby
exploiting the people who currently have Ebola virus disease. The health system should guard against
such situations by providing social support for people who have recovered from Ebola virus disease
and having clear guidelines and regulations against such practices. For example, as suggested in the
WHO interim guidance on community engagement being prepared, communities could consider
providing people who have recovered from Ebola virus disease with integration support packages
containing basic household amenities if these have been destroyed.

3.7 Recipient-related issues

This section outlines ethical issues related to the recipients of convalescent whole blood or plasma
transfusion, whether they are part of a research study or participating in monitored emergency use of
unregistered and experimental interventions.

3.7.1 Fair selection of people with Ebola virus disease

Since the need for transfusion of convalescent whole blood and convalescent plasma may
exceed the available supply, the principles used to set priorities for the intervention should be
agreed through a consultative process. Utilitarian principles suggest that priority should be
given to those who are most likely to benefit from the intervention, or to those who are most
likely to benefit the health system if the treatment is successful. On the other hand, equity
considerations suggest that those who are sicker or those who are more vulnerable, such as
pregnant women and those with diminished autonomy (including children and people with
mental disabilities) should not be arbitrarily excluded from these interventions. Public
engagement and involving relevant stakeholders should be part of the priority-setting activity.
The process used to develop the priority-setting criteria should be fully transparent and
involve the governments of the affected countries or their representatives, a panel of experts
in infectious diseases, transfusion medicine and ethics as well as communities in a

6
WHO has adopted the Code of Ethics for Blood Donation and Transfusion (29).
7
This is in accordance with the principles of voluntary, non-remunerated donation found in the Code of Ethics for Blood
Donation and Transfusion (29).

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 8
 participatory and inclusive manner to avoid creating a perception of unfair allocation,
frustration or public distrust of health systems and health actors, national and/or international.

3.7.2 Autonomy

3.7.2.1 Voluntariness

The ultimate choice of whether to receive convalescent whole blood or convalescent plasma
must rest with the people with Ebola virus disease, and their choice should not affect the care
they would otherwise receive: standard supportive care should always be provided.
Accordingly, people with Ebola virus disease should be given the option to opt out of
treatment with convalescent products at any time. For minors, consent from parents or
guardians and assent from older minors should be obtained. An objection by a minor to take
part in research should generally be respected even if the parents have given permission (35).
However, when the investigational therapy shows promise of therapeutic benefit and there is
no alternative therapy, a parent or guardian may override the child’s objections to participate
(35). When a child who is nearly capable of independent informed consent objects, the
investigator should seek the specific approval of the scientific and ethical review committees
before giving the investigational therapy. Situations of disagreement between the parent or
guardian and the clinician regarding transfusion should be anticipated and mechanisms put in
place to ensure that the child’s well-being is protected.

Given the many children who have lost either one or both parents to Ebola virus disease (36),
parents or guardians may not always be available to consent for the participation of their
children in research. To ensure that orphans are not unfairly excluded from research,
especially if it has potential therapeutic benefit, because they lack an adult representative to
consent for them, countries should appoint responsible committees (such as the ethics
committee or the management committee of the treatment centre) to make the necessary
decisions on a case-by-case basis.

3.7.2.2 Informed consent8

The extent of uncertainty about the efficacy and safety of convalescent whole blood and
convalescent plasma in treating people with Ebola virus disease should be clearly
acknowledged and transparently communicated to each potential person with Ebola virus
disease, whether they are part of a research study or of monitored emergency use of
unregistered and experimental interventions, to avoid fostering unfounded expectations and to
ensure that prospective people with Ebola virus disease make informed decisions regarding
treatment. Information should also be provided to patients with Ebola virus disease regarding
the possible uses of their medical records and of any biological material collected in the
course of the intervention (for research or monitored emergency use of unregistered and
experimental interventions). Further, recipients should be told whether collected data and
biological specimens are planned to be destroyed at the end of the intervention, and if not,
details should be provided about their storage and possible future use. Patients with Ebola
virus disease should have the right to decide about such future use, to refuse storage and to
have the material destroyed. The informed consent of recipients should also be amended if

8
The WHO technical interim guidance on use of convalescent whole blood or plasma collected from patients recovered
from Ebola virus disease for transfusion, as an empirical treatment during outbreaks (30) provides an example of a consent
form for Ebola treatment with experimental convalescent whole blood or plasma therapy.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 9
 new information becomes available that could affect the willingness of subjects to receive
convalescent whole blood or convalescent plasma.

Innovative approaches to the standard informed consent process (such as video or audio
recordings and surrogate consent) may need to be considered to account for the contextual
limitations outlined below.

 Patients are treated in isolation wards, and limited numbers of health-care workers are
allowed inside the treatment area.

 Health-care workers can only spend a limited amount of time inside the treatment area
and are in personal protective equipment, which limits the opportunity for normal
communication-

 The patients’ relatives or next of kin are not allowed inside the treatment area.

 Some patients may be illiterate.

Researchers should anticipate that there will be situations when the person with Ebola virus
disease is unconscious or otherwise too unwell to understand the risk–benefit ratio of these
therapies and obtain prior ethics approval for seeking consent from the next of kin.
Information and possible consent should be considered from the severely sick patient, as soon
as he or she becomes well enough to discuss the treatment. Situations in which a person with
Ebola virus disease is unable to give consent to participate in research and the person’s
representative is not available should be anticipated, and prior ethics approval should be
sought, especially when convalescent whole blood or convalescent plasma is planned to be
given as part of a research trial.

3.7.3 Maintaining a positive risk–benefit ratio for recipients

It is ethically imperative that the risks to people with Ebola virus disease be minimized as
much as possible. Given the uncertain efficacy of using convalescent whole blood and
convalescent plasma in treating patients with Ebola virus disease and given the prevalence of
other transfusion-transmissible infections in the communities where the Ebola virus disease
epidemic is occurring, no shortcuts should be taken in screening donor blood for other
infections and for signs of residual Ebola infectivity (for example, RT-PCR as a surrogate for
infectivity). Complying with safety standards avoids adding risks to an intervention of
unknown benefits and thus maintains a positive benefit–risk balance. Thus, strictly applying
protocols to ensure compatibility between the donor and the recipient and safety regarding
transmissible infections is mandatory. Developing haemovigilance systems to monitor,
investigate, manage and record any adverse transfusion events is also highly recommended.

3.7.4 Confidentiality

The confidentiality of patients with Ebola virus disease should be protected to the maximum
extent possible. In particular, the data and biological samples should be coded (assigning an
ID code or number), and all documents that allow identification should be accessible to
authorized staff only.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 10
3.8 Issues related to health workers and research and ancillary staff

Handling infectious blood samples is associated with several types of risks. Personnel working in
donation and treatment sites therefore need to be provided with adequate safety standards,
including appropriate personal protective equipment. They also need to be adequately trained in
international standard procedures for preventing Ebola virus transmission and for treating patients
with Ebola virus disease with convalescent whole blood and convalescent plasma. Health-care
workers and research and ancillary personnel also need to be well informed about the risks of the
procedures they may undertake and agree to be implementers of these interventions, whether they
are part of research or part of monitored emergency use of unregistered and experimental
interventions. In any case, the risks associated with these procedures need to be minimized as
much as possible.

Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 11
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Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 14
Appendix I
Ethics Working Group Members
Name
Prof Clement Adebamowo
Dr Diallo A Ahmadou
Dr. Juan Pablo Beca
Dr Philippe Calain
Prof Arthur Caplan
Dr Marion Danis
Prof Ogobara Doumbo
Prof Jennifer Gibson
Ryuichi Ida
Dr. Amar Jesani
Robinah Kaitiritimba
Dr Bocar Kouyate
Ethics of using convalescent whole blood and plasma during the Ebola epidemic | 15
Affiliation Country
Chair, National Research Ethics Committee, Nigeria Nigeria
Secretary, Ethics Committee Guinée –
Conakry
Professor, Bioethics Center Universidad del Desarrollo Chile
Senior Researcher, Unit of Research on Humanitarian Switzerland
Stakes and Practices, Médecins Sans Frontières
Drs. William F and Virginia Connolly Mitty Professor USA
Director of the Division of Medical Ethics
NYU Langone Medical Center’s Department of
Population Health
Head, Section on Ethics and Health Policy; Chief, USA
Bioethics Consultation Service, National Institutes of
Health
Director Malaria Research and Training Mali
Centre,University of Bamako, Mali
Sun Life Financial Chair in Bioethics; Director, Joint Canada
Centre for Bioethics;
Associate Professor, Institute of Health Policy,
Management & Evaluation, University of Toronto
Member of the Expert Panel on Bioethics (National Japan
Bioethics Committee), Japan
Independent Researcher and Teacher (Bioethics, Public India
Health); Editor: Indian Journal of Medical Ethics
(https://ijme.in); Visiting Professor: Centre for Ethics,
Yenepoya University, Mangalore.
Community representative, Makerere University IRB; Uganda
Uganda National Health Consumers' Organisation
(UNHCO)
Special advisor to the Minister of Health Burkina
(earlier, Chair of National Ethics Committee); Patient Faso
representative
Prof Bagher Larijiani Director-General, Chief Scientific Officer, Iran
Endocrinology and Metabolism Research Institute;
Acting Director, Medical Ethics and History of
Medicine Research Center, Tehran University of
Medical Sciences, Iran

Prof Melissa Leach Director, Institute of Development Studies United

Kingdom

Dr. Farhat Moazam Founding Chairperson of Center of Biomedical Ethics Pakistan

and Culture, SIUT, Karachi

Prof Cheikh Niang Université Cheikh Anta Diop de Dakar Senegal

Dr. Lisa Schwartz Arnold L. Johnson Chair in Health Care Ethics Canada
Mc Master Ethics in Health Care
McMaster University

Prof Michael Selgelid Director, Centre for Human Bioethics, Monash Australia
University
Dr. Paulina Tindana Ethicist/Senior researcher, Navrongo Health Research Ghana
Centre, Ghana

Prof Oyewale Tomori President, Nigeria National Academy of Sciences Nigeria

Dr Aissatou Touré Head, Immunology Department; Pasteur Institute Senegal

Member, National Ethics Committee

Prof Ross Upshur Canada Research Chair in Primary Care Research Canada
Professor, Department of Family and Community
Medicine and Dalla Lana School of Public Health,
University of Toronto

Cong Yali Associate professor of medical ethics, China

Department of Medical Ethics, Peking University China

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